Recent human clinical application of our epidural spinal cord stimulation (ESCS) technology was found to promote locomotion without fatigue for as long as 300 m with the aid of only a walker in a SCI patient. Our previous studies had shown that ESCS in acutely transected animals induced treadmill stepping. More recently, we found that passive exercise training in adult spinal cord transected rats led to maintenance of muscle mass (i.e. prevented muscle atrophy) and restored habituation of the H-reflex (i.e. decreased hyperreflexia). The proposed research is designed to develop a SCI Mobilization Program for humans, at first testing partial weight bearing training (PWBT) and motorized bicycle exercise training (MBET) for their effects, singly and in combination, on locomotor activity and H-reflex habituation in SCI patients. We will measure and compare increases in muscle mass, improvements in step cycle parameters, changes in motor and sensory indices, and changes in H-reflex habituation and spasticity. Future studies will include ESCS and other potential therapies. We will also test in animals additional potential palliative strategies for SCI. Recently, we tested successfully the possibility of combining 1) MBET, 2) ESCS and 3) oral L-dopa therapy to promote locomotion in transected adult rats. Preliminary data indicate that this combination of therapies may prove efficacious in the restoration of stepping following complete spinal transection in the rat. The variable to be measured is electromyographic (EMG) activity in the hindlimbs, with analysis of muscle burst timing and amplitude, and step cycle frequency and duration, induced following each form of treatment or combined therapy. Data will be generated using an established model of SCI in the rat. These studies will provide essential information regarding the optimal combination of pharmacological intervention, exercise duration, and electrical stimulation parameters of the spinal cord necessary to maximize recovery of spinal locomotion following SCI. There is great potential for such information to translate into improved rehabilitation strategies for the human patient with SCI. An indirect benefit of these therapies may be the reduction of hyperreflexia, and presumably spasticity, in some patients with SCI (with concomitant reduction in baclofen therapy). The proposed research will generate pilot data in multiple important areas for securing future R01 support.